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Biomedical subjects

A Fein

Publications and source records attributed to A Fein.

At least 91 records · Page 5Linked to original sources
PubMed1987

Teratogenic effect of D-amphetamine sulphate: histodifferentiation and electrocardiogram pattern of mouse embryonic heart.

Pregnant albino mice (ICR random-bred strain) received daily injections of 50 or 100 mg/kg body weight of D-amphetamine sulphate between days 9 and 11 of gestation. Parallel control animals were injected with saline solution. Treated mice were sacrificed on day 15 or 19 of gestation. The embryos were examined for gross malformations and direct embryonic ECG recordings were made; they were weighed, and their hearts were carefully dissected. Microscopic sections of the heart were stained with hematoxylin and eosin. It was found that high doses of D-amphetamine raised the incidence of mortality in the treated pregnant mice up to 40%. The resorption rate in the survivors was high (up to 58%) following the high dose of the drug. Up to 15% of the embryos from the treated groups showed gross malformations, including skeletal and eye malformations and exencephaly. The electrocardiogram (ECG) recordings in most 19-day-old embryos from both treated groups showed a pattern with prolonged Q-T interval (PQT), similar to that of control embryos in the intermediate developmental stages (days 14-16 of gestation). The ECG of control embryos (from day 17 on) resembled that of prenatal fetuses. Microscopically, the hearts of treated embryos showed a large number of undifferentiated cardiac myoblasts. It can be inferred that high doses of D-amphetamine affect embryonic development generally and delay the histodifferentiation of the myocardium, resulting in incomplete maturation of the cardiac muscles, thus leading to the immature ECG pattern, with PQT intervals.

Abnormalities, Drug-Induced↗
PubMed1987

Inositol 1,4,5 trisphosphate releases calcium from specialized sites within Limulus photoreceptors.

We have investigated the subcellular distribution and identity of inositol trisphosphate (InsP3)-sensitive calcium stores in living Limulus ventral photoreceptor cells, where light and InsP3 are known to raise intracellular calcium. We injected ventral photoreceptor cells with the photoprotein aequorin and viewed its luminescence with an image intensifier. InsP3 only elicited detectable aequorin luminescence when injected into the light-sensitive rhabdomeral (R)-lobe where aequorin luminescence induced by light was also confined. Calcium stores released by light and InsP3 are therefore localized to the R-lobe. Within the R-lobe, InsP3-induced aequorin luminescence was further confined around the injection site, due to rapid dilution and/or degradation of injected InsP3. Prominent cisternae of smooth endoplasmic reticulum are uniquely localized within the cell beneath the microvillar surface of the R-lobe (Calman, B., and S. Chamberlain, 1982, J. Gen. Physiol., 80:839-862). These cisternae are the probable site of InsP3 action.

Aequorin↗
PubMed1987

Lectin receptors on preimplantation mouse embryos. The solidity of lectin binding.

Receptor sites for 7 FITC-conjugated lectins were examined on preimplantation mouse embryos at various stages of development: zygotes; 2; 6-8 cells; morulae; blastocyst; expanded blastocyst, and isolated inner cell mass. In order to determine the solidity of the binding, the embryos were incubated with lectins, washed and incubated for an additional time with the specific hapten sugar. Receptor sites for all 7 lectins were found on the cell surface of all preimplantation mouse embryonic stages examined. The binding was found to be specific. The solidity of the lectins' binding to the receptors was found to be high, since it could not be removed by the corresponding sugar hapten.

Animals↗
PubMed1987

Angiotensin converting enzyme in bronchoalveolar lavage in ARDS.

Angiotensin converting enzyme (ACE) is present in the endothelial cells of the normal lung where it converts angiotensin I to angiotensin II and inactivates bradykinin. It has been suggested that during endothelial injury ACE is sloughed into the blood, and that if the alveolar capillary membrane is injured, also into the alveolar lining fluid. Seven patients with adult respiratory distress syndrome (ARDS), were compared to 11 normal control subjects, nine patients with sarcoidosis, and six with idiopathic pulmonary fibrosis. Total, differential cell counts and ACE determinations were performed on bronchoalveolar lavage fluid in the ARDS group. ACE was detectable in the BAL of all but one ARDS patient. It was concluded that BAL ACE is elevated in some ARDS patients, especially those with infectious causes of lung injury. Increased ACE may reflect endothelial damage or local increase in ACE production in response to sepsis.

Adult↗
PubMed1986

Light stimulates the rapid formation of inositol trisphosphate in squid retinas.

To test the hypothesis that inositol trisphosphate (InsP3) mediates adaptation and excitation in invertebrate photoreceptors, we measured its formation on a rapid time scale in squid retinas. For squid, excitation and adaption occurs within 0.1 and 1-2 s respectively. We could detect an elevation in InsP3 within 200 ms of a bright flash. This increase is about 240% over dark basal levels and is maintained for at least 2 min after a flash. The increase probably occurs in the photoreceptors, which are the only neurons in squid retinas. Analysis by h.p.l.c. indicates that the light-regulated isomer is Ins(1,4,5)P3, which is formed by the hydrolysis of phosphatidylinositol bisphosphate (PtdInsP2).

Animals↗
PubMed1986

Blockade of visual excitation and adaptation in Limulus photoreceptor by GDP-beta-S.

Light causes both depolarization and adaptation to light in Limulus ventral photoreceptors. Both visual excitation and adaptation were blocked by guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S), a metabolically stable analog of guanosine 5'-diphosphate (GDP). However, GDP-beta-S did not block the excitation caused by injection of inositol 1,4,5-trisphosphate into the cell. These results suggest a molecular cascade of visual excitation and adaptation: Light isomerizes the visual pigment rhodopsin, which in turn activates a guanyl nucleotide-binding protein. The binding protein then stimulates production of inositol 1,4,5-trisphosphate, which causes release of calcium from the endoplasmic reticulum.

Adaptation, Ocular↗
PubMed1986

Localization of the photocurrent of Limulus ventral photoreceptors using a vibrating probe.

We have used a vibrating probe to determine the profile of electrical current density around ventral photoreceptors of the horseshoe crab following flashes of light that uniformly illuminated the entire surface of the photoreceptor's cell body. The vibrating probe signal indicated that the density of inward current was greatest at the distal region of the cell, the region that is expected to contain the light-sensitive rhabdom. The density of inward current typically declined at the midpoint of the cell body and then reversed to an outward current flow in the proximal region of the cell body, close to the axon. The profile of local sensitivity of the photoreceptor to light closely matched the profile of inward current density, suggesting that the light-activated conductance is localized to the light-sensitive region of the cell.

Animals↗
PubMed1986

Regulation of cortical vesicle exocytosis in sea urchin eggs by inositol 1,4,5-trisphosphate and GTP-binding protein.

To investigate the roles of inositol 1,4,5-trisphosphate (InsP3) and guanyl nucleotide binding proteins (G-proteins) in the transduction mechanism coupling fertilization and exocytosis of cortical vesicles in sea urchin eggs, we microinjected InsP3 and guanyl nucleotide analogs into eggs of Lytechinus variegatus. Injection of 28 nM InsP3 caused exocytosis. However, if the egg was first injected with EGTA ([Cai] less than or equal to 0.1 microM; EGTA = 1.6 mM), InsP3 injection did not cause exocytosis, supporting the hypothesis that InsP3 acts by causing a rise in intracellular free calcium. Injection of 28 microM guanosine-5'-0-(3-thiotriphosphate) (GTP-gamma-S), a hydrolysis-resistant analog of GTP, caused exocytosis, but exocytosis did not occur if the egg was pre-injected with EGTA. Injection of 3 mM guanosine-5'-0-(2-thiodiphosphate) (GDP-beta-S), a metabolically stable analog of GDP, prevented sperm from stimulating exocytosis. However, injection of GDP-beta-S did not prevent the stimulation of exocytosis by InsP3. These results suggested the following sequence of events. The sperm activates a G-protein, which stimulates production of InsP3. InsP3 elevates intracellular free calcium, which causes exocytosis.

Animals↗
PubMed1986

The initial response of Limulus ventral photoreceptors to bright flashes. Released calcium as a synergist to excitation.

The leading edge of the response of Limulus ventral photoreceptors to brief flashes was investigated using a voltage clamp. The leading edge of responses increases linearly with flash intensity when dim flashes produce less than one photoisomerization per square micron of cell surface. Brighter flashes accelerate the initial portion of the response, resulting in a fourth-power relationship between the magnitude of the response at brief times after the flash and the flash intensity. The onset of this nonlinearity with increasing flash intensity is determined by the local density of photoisomerizations within the receptor. Responses to bright 10-15-mum-diam spots therefore rise faster than responses to diffuse flashes producing the same number of photoisomerizations within the receptor. Background illumination shortens the response latency and suppresses the initial nonlinearity. These phenomena can be explained by a model of transduction in which light activates two parallel cascades of reactions. Particles released by the first of these cascades open ionic channels, while the second produces an agent that accelerates the rate of production of particles by the first. Injection of the calcium buffer EGTA slows the initial portion of the response to bright flashes and suppresses its nonlinearity, which suggests that the accelerating agent released by the second cascade is calcium.

Animals↗
PubMed1986

Pressure injection of calcium both excites and adapts Limulus ventral photoreceptors.

Single pressure injections of 1-2 mM calcium aspartate into the light-sensitive region of Limulus ventral photoreceptors resulted in a rapid, 20-40-mV depolarization lasting approximately 2 s. The depolarization closely followed the rise in intracellular free calcium caused by the injection, as indicated by aequorin luminescence. The depolarization was followed by reversible desensitization (adaptation) of responses to both light and inositol 1,4,5 trisphosphate. Similar single injections of calcium into the light-insensitive region of the receptor were essentially without effect, even though aequorin luminescence indicated a large, rapid rise in intracellular free calcium. The depolarization caused by injection of calcium arose from the activation of an inward current with rectification characteristics and a reversal potential between +10 and +20 mV that were similar to those of the light-activated conductance, which suggests that the same channels were activated by light and by calcium. The reversal potentials of the light- and calcium-activated currents shifted similarly when three-fourths of the extracellular sodium was replaced by sucrose, but were not affected by a similar replacement of sodium by lithium. The current activated by calcium was abolished by prior injection of a calcium buffer solution containing EGTA. The responses of the same cells to brief light flashes were slowed and diminished in amplitude, but were not abolished after the injection of calcium buffer. Light adaptation and prior injection of calcium diminished the calcium-activated current much less than they diminished the light-activated current.

Adaptation, Physiological↗
PubMed1986

Excitation and adaptation of Limulus ventral photoreceptors by inositol 1,4,5 triphosphate result from a rise in intracellular calcium.

Single pressure injections of 1-10 pl of inositol 1,4,5 triphosphate (IP3) or inositol 4,5 bisphosphate [I(4,5)P2] excite Limulus ventral photoreceptors by inducing rapid bursts of inward current. After excitation by IP3, responses to subsequent injections of IP3 or light flashes are often reversibly diminished (adapted). Single injections of IP3 and I(4,5)P2 are effective at concentrations in the injecting pipette of 20 microM to 1 mM. Single injections of inositol 1,4 bisphosphate are ineffective at concentrations of 100-500 microM. Excitation by IP3 or I(4,5)P2 is accompanied by a rise in intracellular free calcium, as indicated by aequorin luminescence. Prior injection of calcium buffer solutions containing 100 mM EGTA greatly diminishes the total charge transferred across the plasma membrane during excitation by IP3 or I(4,5)P2, which suggests that a rise in Cai is necessary for excitation by the inositol polyphosphates. Adaptation of the response to light by IP3 is also abolished by prior injection of EGTA. In the same cells, the response to brief light flashes is slowed and diminished in amplitude by the injection of calcium buffer, but the charge transferred during the response is not significantly diminished. This suggests that light has access to a pathway of excitation in the presence of EGTA that is not accessible to intracellularly injected IP3.

Adaptation, Physiological↗
PubMed1986

Pathophysiology of the adult respiratory distress syndrome. What have we learned from human studies?

Clinical studies of ARDS have been successful in determining the most common predisposing clinical disorders and the natural history of this syndrome. Sepsis, gastric aspiration, and major trauma are the most frequently associated high-risk factors. Overall mortality is in the range of 60% to 70%, but is even higher if ARDS is associated with sepsis, severe acidemia, or decreased renal function. It is evident that multisystem failure is responsible for death in many patients, as well as secondary pulmonary and extrapulmonary infections. Pathologic studies have provided descriptive information regarding the acute, subacute, and chronic phases of the syndrome, but little insight into the precise pathogenesis of the initial lung injury or the progressive fibrosing alveolitis and lung destruction that develops in some patients. There has been considerable circumstantial evidence from clinical studies implicating the neutrophil as a potentially important mediator of the early changes in lung endothelial and epithelial permeability. However, not all investigators have found the same alterations in neutrophil function in the circulation or in the lavage from the lungs of patients with ARDS. Also, the heterogeneous etiologies of ARDS make it difficult to be sure that there is a final common pathway for acute lung injury in all ARDS patients. In addition, there are a host of mediators, including products of complement activation and arachidonic acid metabolism, that may be important in amplifying the inflammatory response. Also, abnormalities of surfactant production and collagen turnover, as well as impaired host defenses in the lung, may contribute to the progressive respiratory failure that occurs in some ARDS patients, even though the acute, exudative phase of lung injury has resolved. Future human studies may provide useful information about the mechanisms of the acute lung injury through studies of circulating plasma markers, blood elements, and lavage fluids from high-risk patients. On the other hand, samples of cells and mediators from the airspaces with lavage still may not reflect the critical interactions of mediators and cells with the lung endothelium that lead to the protein-rich pulmonary edema that characterizes the first phase of ARDS. Thus, experimental studies must continue to study the details of the early phases of acute lung injury (see article by Flick, page 455). Finally, it is clear that treatment designed to reduce the severity and the incidence of ARDS must be started early, since the syndrome develops so rapidly in high-risk patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Platelets↗
PubMed1985

Relationship between light sensitivity and intracellular free Ca concentration in Limulus ventral photoreceptors. A quantitative study using Ca-selective microelectrodes.

The possible role of Ca ions in mediating the drop in sensitivity associated with light adaptation in Limulus ventral photoreceptors was assessed by simultaneously measuring the sensitivity to light and the intracellular free Ca concentration (Cai); the latter was measured by using Ca-selective microelectrodes. In dark-adapted photoreceptors, the mean resting Cai was 3.5 +/- 2.5 microM SD (n = 31). No correlation was found between resting Cai and absolute sensitivity from cell to cell. Typically, photoreceptors are not uniformly sensitive to light; the Cai rise evoked by uniform illumination was 20-40 times larger and faster in the most sensitive region of the cell (the rhabdomeral lobe) than it was away from it. In response to a brief flash, the Cai rise was barely detectable when 10(2) photons were absorbed, and it was saturated when approximately 10(5) photons were absorbed. During maintained illumination, starting near the threshold of light adaptation, steady Cai increases were associated with steady desensitizations over several log units of light intensity: a 100-fold desensitization was associated with a 2.5-fold increase in Cai. After a bright flash, sensitivity and Cai recovered with different time courses: the cell was still desensitized by approximately 0.5 log units when Cai had already recovered to the prestimulus level, which suggests that under those conditions Cai is not the rate-limiting step of dark adaptation. Ionophoretic injection of EGTA markedly decreased the light-induced Cai rise and increased the time to peak of the light response, but did not alter the resting Cai, which suggests that the time to peak is affected by a change in the capacity to bind Ca2+ and not by resting Cai. Lowering the extracellular Ca2+ concentration (Cao) first decreased Cai and increased sensitivity. Longer exposure to low Cao resulted in a further decrease of Cai but decreased rather than increased sensitivity, which suggests that under certain conditions it is possible to uncouple Cai and sensitivity.

Animals↗
PubMed1985

Cell lineage evaluation in preimplantation mouse embryos by intracellular injection of IgG.

The cell lineage in preimplantation mouse embryos was studied by injecting rabbit IgG into zygotes or into a blastomere of early or late 2-cell, 3- or 4-cell stage embryos. The localization of the IgG was detected by the peroxidase-antiperoxidase method. It was found that starting from the late 2-cell stage, lineage could be followed up to the cell populations of the blastocyst, inner cell mass and trophectoderm.

Animals↗
PubMed1985

Collagenase in the lower respiratory tract of patients with adult respiratory distress syndrome.

Collagenase activity in the bronchoalveolar lavage (BAL) of patients with adult respiratory distress syndrome (ARDS) was measured against Type I collagen (17 patients) and against Type III collagen (13 patients). Serine protease activity was also measured against Type III collagen (13 patients). Type I collagenase activity was detectable in 12 of 17 and Type III collagenase was detectable in 12 of 13 patients with ARDS. The 10 control subjects had no detectable Types I or III collagenase activity. Total and differential white cell counts were analyzed in the lavage fluid. Although the total counts did not differ between patients with ARDS and control subjects, the percentage of neutrophils was increased more than 25-fold and the percentage of macrophages was reduced almost 10-fold in the ARDS patients. Serial collagenase activity was followed in 1 ARDS survivor. In this patient Type III collagenase activity peaked before the Type I collagenase activity or serine protease activity reached their maximums. Both the latter enzyme activities paralleled the total recoverable cells in the BAL.

Adult↗
PubMed1985

Neutrophil elastase-releasing factors in bronchoalveolar lavage from patients with adult respiratory distress syndrome.

Bronchoalveolar lavage fluid (BAL) was obtained from patients with adult respiratory distress syndrome (ARDS). Controls included BAL from normal subjects and from patients with sarcoidosis or pulmonary fibrosis. Neutrophil elastase measured immunologically was found in all BAL samples, but it was strikingly greater in BAL from patients with ARDS than in the BAL from normal subjects or patients with sarcoidosis. There was no significant difference in the neutrophil elastase antigen concentrations in BAL samples from patients with ARDS and those with pulmonary fibrosis. No elastolytic activity was found in either group. The alpha-1-antitrypsin and the bronchial mucus inhibitor were greater in BAL from patients with ARDS. There was a highly significant correlation between the alveolar-arterial oxygen tension difference and the neutrophil elastase concentration in BAL from the patients with ARDS. Kallikrein, prekallikrein, factor XIa-like activity, and high molecular weight kininogen antigen were found in BAL of patients with ARDS, suggesting that the kallikrein-kinin cascade may be activated in the lungs of patients with ARDS. Kallikrein-like activity in the BAL from the patients with ARDS was significantly correlated with the number of neutrophils in the BAL, the neutrophil elastase concentration, and the ability of the BAL to release elastase from cytochalasin-B-treated neutrophils. There was no correlation between these variables and C5a concentration. These studies demonstrated an association between BAL neutrophil elastase and the clinical state of patients with ARDS.

Adult↗
PubMed1984

Absorptance and spectral sensitivity measurements of rod photoreceptors of the tiger salamander, Ambystoma tigrinum.

The spectral sensitivity of the extracellularly-recorded photoresponse of isolated rods of the tiger salamander, Ambystoma tigrinum, was compared to the absorptance spectrum. Both measurements were made with the same optical system on the same portion of each cell to avoid errors that could occur when the two kinds of measurement were made under different conditions. The relative spectral sensitivity and absorptance spectrum were found to be in excellent agreement between 450 and 700 nm.

Ambystoma↗